POS1259 SYSTEMIC SCLEROSIS AND COVID-19 VACCINE-ASSOCIATED DELAYED ADVERSE EVENTS: INSIGHTS FROM THE COVAD-2 STUDY
Authors: B. Doskaliuk, P. Sen, M. Joshi, N. Ravichandran, A. L. Tan, S. Katsuyuki Shinjo, S. Saha, N. Ziade, T. Chatterjee, M. Kuwana, J. Knitza, O. Distler, R. Aggarwal, A. Makol, L. Gupta, V. Agarwal
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> We have previously reported short term safety of the COVID-19 vaccination in patients with Systemic sclerosis (SSc) but delayed adverse events (ADEs) (occurring &gt;7 days post-vaccination) are poorly characterized in this rare yet vulnerable disease group. <h3>Objectives</h3> We analyzed delayed COVID-19 vaccine-related ADEs among patients with SSc, other systemic autoimmune and inflammatory disorders (SAIDs) and healthy controls (HC) using data from the ongoing 2<sup>nd</sup> global COVID-19 Vaccination in Autoimmune Diseases (COVAD-2) study [1]. <h3>Methods</h3> The COVAD-2 study was a cross-sectional, patient self-reporting e-survey utilizing an extensively validated, pilot tested questionnaire, translated into 19 languages, circulated by a group of 157 physicians across 106 countries from February to June 2022. We captured data on demographics, SSc/SAID disease characteristics (including skin subset, treatment history and self-reported disease activity), autoimmune and non-autoimmune comorbidities, COVID-19 infection history and course, and vaccination details including delayed ADEs as defined by the CDC. Delayed ADEs were categorized into local injection site pain/soreness; minor and major systemic ADEs, and hospitalizations. We descriptively analyzed the risk factors for overall and specific ADEs in SSc and SAIDs, and further triangulated clinically significant variables in binominal logistic regression analysis with adjustment for age, gender, ethnicity, comorbidity, and immunosuppressive therapy to analyze the survey responses. <h3>Results</h3> From among 17 612 respondents, 10 041 patients (median age 51 (18-58) years, 73.4% females, 44.9% Caucasians) vaccinated against COVID-19 at least once (excluding incomplete responses and trial participants) were included for analysis. Of these, 2.6 % (n=258) had SSc, 63.7% other SAIDs, and 33.7% were HCs. BNT162b2 Pfizer (69.4%) was the most administered vaccine, followed by MRNA-1273 Moderna (32.25%) and ChadOx1 nCOV-19 Oxford/AstraZeneca (12.4%) vaccines. Among the patients with SSc, 18.9% reported minor while 8.5% experienced major delayed ADEs, and 4.6% reported hospitalization. These values were comparable to those of the ADEs reported in other SAIDs and HCs. Patients with SSc reported higher frequency of difficulty in breathing than HCs [OR=2.3 (1.0-5.1), p=0.042]. Individuals receiving Oxford/AstraZeneca reported more minor ADEs [OR=2.5 (1.0-6.0), p=0.045]; whereas patients receiving Moderna were less likely to develop myalgia and body ache [OR=0.1 (0.02-1.0), p=0.047 and OR=0.2 (0.05-1.0), p=0.044 respectively]. Patients with diffuse cutaneous SSc experienced minor ADEs and specifically fatigue more frequently [OR=2.1 (1.1-4.4), p=0.036, and OR=3.9 (1.3-11.7), p=0.015] than those with limited cutaneous SSc. Self-reported active disease pre-vaccination did not confer any increased risk of vaccine ADEs in the adjusted analysis. Unlike our previous observations in myositis, autoimmune and non-autoimmune comorbidities did not affect the risk of delayed ADEs in SSc. SSc patients with concomitant myositis reported myalgia [OR=3.4 (1.1-10.7), p=0.035] more frequently, while those with thyroid disorders were more prone to report a higher frequency of joint pain [OR=5.5 (1.5-20.2), p=0.009] and dizziness [OR=5.9 (1.3-27.6), p=0.024] than patients with SSc alone. Patients with SSc-interstitial lung disease did not report increased frequency of ADEs. <h3>Conclusion</h3> A diagnosis of SSc did not confer a higher risk of delayed post COVID-19 vaccine-related ADEs than other SAIDs and HCs. Diffuse cutaneous phenotype and certain co-existing autoimmune conditions including myositis and thyroid disease can increase the risk of minor ADEs. These patients may benefit from pre-vaccination counselling, close monitoring, and early initiation of appropriate care in the post COVID-19 vaccination period. <h3>Reference</h3> [1]Fazal ZZ, Sen P, Joshi M, Ravichandran N, Lilleker JB, et al. COVAD survey 2 long-term outcomes: unmet need and protocol. Rheumatol Int 2022 Dec; 42(12):2151-2158 <h3>Acknowledgements</h3> COVAD Study Team. <h3>Disclosure of Interests</h3> Bohdana Doskaliuk: None declared, Parikshit Sen: None declared, Mrudula Joshi: None declared, Naveen Ravichandran: None declared, Ai Lyn Tan Speakers bureau: Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, Samuel Katsuyuki Shinjo: None declared, Sreoshy Saha: None declared, Nelly Ziade Speakers bureau: Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre, Consultant of: Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre, Grant/research support from: Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and. Pierre Fabre, Tulika Chatterjee: None declared, Masataka Kuwana: None declared, Johannes Knitza: None declared, Oliver Distler Speakers bureau: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Consultant of: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Grant/research support from: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Rohit Aggarwal Consultant of: Mallinckrodt, Octapharma, CSL Behring, Bristol Myers-Squibb, EMD Serono, Kezar, Pfizer, AstraZeneca, Alexion, Argenx, Boehringer Ingelheim, Corbus, Janssen, Kyverna, Roivant, Merck, Galapagos, Actigraph, Abbvie, Scipher, Horizontal Therapeutics, Teva, Biogen, Beigene, ANI Pharmaceutical, Nuvig, Capella, CabalettaBio, Grant/research support from: Mallinckrodt, Pfizer, Bristol Myers-Squibb, Q32, EMD Serono, Janssen, Boehringer Ingelheim (BI), Ashima Makol: None declared, Latika Gupta: None declared, Vikas Agarwal: None declared.